Abstract
BackgroundRecently, the pesudogenes have emerged as critical regulators in human cancers tumorigenesis and progression, and been identified as a key revelation in post-genomic biology. However, the expression pattern, biological function and mechanisms responsible for these molecules in human gastric cancer (GC) are not fully understood.MethodsIn this study, we globally assessed the transcriptomic differences of pesudogenes in gastric cancer using publicly available microarray data. DUXAP10 expression levels in GC tissues and cells was detected using quantitative real-time PCR (qPCR). DUXAP10 siRNAs and over-expression vector were transfected into GC cells to down-regulate or up-regulate DUXAP10 expression. Loss- and gain-of function assays were performed to investigate the role of DUXAP10 in GC cells cell proliferation, and invasion. RIP, RNA pulldown, and ChIP assays were used to determine the mechanism of DUXAP10’s regulation of underlying targets.ResultsThe pesudogene DUXAP10 is the only pseudogene that significantly over-expressed in all four GEO datasets, and frequently over-expressed in many other cancers including Liver Hepatocellular carcinoma, Bladder cancer, and Esophageal Cancer. High DUXAP10 expression is associated with GC patients poor prognosis, and knockdown of DUXAP10 significantly inhibits cells proliferation, migration and invasion in GC. Mechanistic investigation shows that DUXAP10 can interact with PRC2 and LSD1 to repress LATS1 expression at transcriptional level, and bind with HuR to maintain the stability of β-catenin mRNA and increase its protein levels at post-transcriptional level.ConclusionsOverall, our findings illuminate how increased DUXAP10 confers an oncogenic function in GC development and progression that may serve as a candidate prognostic biomarker and target for clinical management of GC.
Highlights
The pesudogenes have emerged as critical regulators in human cancers tumorigenesis and progression, and been identified as a key revelation in post-genomic biology
The GSE54129 dataset consists of 21 normal, and 111 gastric cancer (GC) samples; GSE70880 consists of 20 paired samples; GSE79973 consists of 10 paired samples; GSE99416 consists of 6 paired samples
Re-annotation and analysis of these data revealed that 707 pseudogenes expression were dysregulated in the GSE54129 dataset (354 upregulated and 353 downregulated); 53 pseudogenes were dysregulated in the GSE70880 dataset (33 upregulated and 20 downregulated); 144 pseudogenes expression were dysregulated in the GSE79973 dataset (52 upregulated and 92 downregulated); and 184 pseudogenes were differentially expressed in the GSE99416 dataset (67 upregulated and 77 downregulated) (Fig. 1a-d, and Additional file 2: Table S2)
Summary
The pesudogenes have emerged as critical regulators in human cancers tumorigenesis and progression, and been identified as a key revelation in post-genomic biology. The expression pattern, biological function and mechanisms responsible for these molecules in human gastric cancer (GC) are not fully understood. There are a great advancement on the gastric carcinogenesis, the molecular mechanisms underlying gastric cancer progression and tumor metastasis are still poorly understood [4]. Benefiting from the advancement on bioinformatics and generation sequencing technique, the completion of the ENCODE (Encyclopedia of DNA Elements) project and FANTOM (Functional Annotation of Mammals) consortia has highlighted the prevalence of non-protein coding functional elements in human genome [5, 6]. Increasing evidence reveales the multilayered biological function of pseudogenes in diverse cellular processes, especially their contribution to human cancers by acting as endogenous competitors for miRNA, generating endogenous smallinterference RNA (endo-siRNA or esiRNA) or through competing for RNA-binding protein (RBP) or translational machinery [12, 13]
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